The overall objective of this proposed research project is to obtain basic information on the lung's role in drug metabolism and disposition. This will involve a study of the microsomal drug- metabolizing enzymes (mixed-function oxidases) of lung tissue and will be approached with five specific aims: 1. The metabolic pathways of chlorcyclizine, amphetamine, and imipramine will be determined in vitro with lung microsomes. 2. The rates of biotransformation of chlorcyclizine, amphetamine, or imipramine via their various metabolic pathways will be determined with lung microsomes in vitro. 3. The relationship between the extent of drug localization and the extent of drug metabolism in the lung will be explored for chlorcyclizine, amphetamine, or imipramine. 4. The effect of enzyme induction on drug localization in lung tissue and rates of pulmonary drug metabolism will be investigated. 5. Lung tissue will be dispersed into individual viable cells, and this preparation will be evaluated as a new model for the study of drug metabolism in lung in vitro. The results of these studies will be considered in light of their therapeutic and toxicological implications and as an indication of the overall influence of the lung on drug metabolism and disposition in vivo.